Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with the acquired immunodeficiency syndrome (AIDS) and occurs in an estimated 25% of these patients. Untreated, CMV retinitis is a relentlessly progressive condition, the end result of which is total destruction of the retina and complete blindness. Treatment with either ganciclovir or foscarnet results in arrest of the progression of CMV retinitis in 80% to 90% of cases. Neither drug is curative, and long-term suppressive therapy (maintenance) is required; discontinuation of antiCMV therapy results in reactivation of the retinitis within three weeks. Despite continued long-term maintenance therapy, reactivation of the retinitis will occur in all patients given enough time. Potential reasons for reactivation of the retinitis despite chronic maintenance therapy (breakthrough) include the declining immune system in patients with AIDS and the development of resistance of CMV to the anti-CMV drug used. Previous studies of patients treated with ganciclovir for CMV retinitis have demonstrated the development of virus culturable from the urine which is resistant to ganciclovir in up to 38% of patients treated for over three months. These studies have shown a correlation between duration of ganciclovir therapy and the development of resistance. However, the relationship between the resistant virus in the urine and the behavior of the intraocular infection has not been explored. We have previously demonstrated that in selected cases where the retinitis is relapsing at a rate suggesting poor efficacy of the anti-CMV drug being employed, virus can be cultured from the blood and/or urine which is resistant to the anti-CMV agent. However, this study looked selectively at patients where resistance was likely; the magnitude of the problem of viral resistance remains unknown. In order to address issues relating to CMV retinitis and the development of viral resistance to anti-CMV agents, a cohort of 280 patients will be followed prospectively for the development of drug resistance. Cultures of blood and urine will be taken at the time of diagnosis of CMV retinitis , at regular intervals while on therapy, and at times of breakthrough. Progression of CMV retinitis will be assessed in a masked fashion using a fundus photography reading center. The' study will determine: 1) the incidence and prevalence of resistant CMV; 2) risk factors for the development of resistant CMV (e.g. duration of anti-CMV therapy); and 3) the relationship between viral resistance and clinical outcome.